Regulation of fetal cardiac and hepatic β-adrenoceptors and adenylyl cyclase signaling: Terbutaline effects
Terbutaline (Ter), a β2-adrenergic agonist used in preterm labor, stimulates fetal β-adrenoceptors (β-ARs). We administered Ter to pregnant rats on gestational days 17-20 and examined β-ARs and adenylyl cyclase (AC) signaling in heart and liver. Ter produced less downregulation of cardiac β-ARs than in adults, despite a higher proportion of the β2-subtype, and failed to elicit desensitization of the receptor-mediated AC response. AC stimulants acting at different points indicated an offsetting of homologous desensitization at the level of the β-AR by heterologous sensitization at the level of AC: induction of total AC catalytic activity and a shift in the catalytic profile or AC isoform. In fetal liver, Ter produced downregulation of β-ARs, in keeping with the predominance of the β2-subtype; hepatic receptor downregulation was equivalent in fetus and adult. Nevertheless, there was still no desensitization of β-AR-mediated AC responses and again AC was induced. Our results indicate that, unlike in the adult, fetal β-AR signaling is not desensitized by β-agonists and, in fact, displays heterologous sensitization, thus sustaining responses during parturition. At the same time, the inability to desensitize β-AR AC responses may lead to disruption of cardiac, hepatic, or neural cell development as a consequence of tocolytic therapy with β-agonists.
Auman, JT; Seidler, FJ; Slotkin, TA
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